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Journal of Clinical Oncology editorial: “Compelling” evidence acupuncture “may be” effective for cancer related fatigue

Journal of Clinical Oncology (JCO) is a high impact journal (JIF > 16)  that advertises itself as a “must read” for oncologists. Some cutting edge RCTs evaluating chemo and hormonal therapies have appeared there. But a past blog post gave dramatic examples of pseudoscience and plain nonsense to be found in JCO concerning psychoneuroimmunology (PNI) and, increasingly, integrative medicine and even integrations of integrative medicine and PNI. The prestige of JCO has made it a major focus for efforts to secure respectability and third-party payments for CAM treatments by promoting their scientific status and effectiveness.

Once articles are published in JCO, authors can escape critical commentary by simply refusing to respond, taking advantage of an editorial policy that requires a response in order for critical commentaries to be published. An author’s refusal to respond means criticism cannot be published.

Some of the most outrageous incursions of woo science into JCO are accompanied by editorials that enjoy further relaxation of any editorial restraint  and peer review. Accompanying editorials are a form of privileged access publishing, often written by reviewers who have strongly recommended the article for publication, and having their own PNI and CAM studies to promote with citation in JCO.

Because of strict space limitations, controversial statements can simply be declared, rather than elaborated in arguments in which holes could be poked. A faux authority is created. Once claims make it into JCO, their sources are forgotten and only the appearance a “must read,” high impact journal is remembered. A shoddy form of scholarship becomes possible in which JCO can be cited for statements that would be recognized as ridiculous if accompanied by a citation of the origin in a CAM journal. And what readers track down and examine original sources for numbered citations, anyway?

A recent article concerning a RCT of acupuncture for cancer related fatigue (CRF) was accompanied by an editorial by Julienne Bower, who lists her affiliation as the Cousins Center for Psychoneuroimmunology of UCLA. The editorial is more transparent than most in displaying some rhetorical, i.e., marketing, strategies for PNI and CAM. This blog, I will show what tricks can be uncovered in a close read, things to be alert for when decoding and debunking promotions of PNI and CAM.

The editorial’s opening paragraph declares that “up to 99% of patients experience some level fatigue” and the paragraph suggests fatigue may last “for 10 years or more” and ends with the tie-in of fatigue with recurrence-free and overall survival time.

Okay, CRF is a common complaint, but the “up to 99%” depends on a dubious stretching of the prevalence of fatigue with the highest of the high estimates that depend on the lowest of the low thresholds for counting patients as fatigued. Similarly, for the “10 years or more.” And the tying of fatigue to prognosis and survival is classic PNI hype. Correlation is not causality, and in this instance any association may even be reverse causality, with persistent fatigue indicating disease processes that can be related to prognosis and survival. There is hedging here with the “up to” and “10 years or more, but the foundation is being laid for the familiar, but unsubstantiated claims of CAM and PNI-derived techniques that influence the course and outcome of cancer.

The message is ‘Fatigue is common, sometimes long-lasting, and can accelerate progression of your cancer and shorten your life, but now we are going to talk about something you can do about it.’ There is only a string of juxtapositions here, not a formal argument that can be disputed. In the larger literature, there has been no demonstration that altering PNI response has an influence on course or survival time or even identification of a plausible mechanism by which this effect could occur. But the message comes through and finds a receptive audience in vulnerable cancer patients hungry for something they can do to take control of their disease.

The next paragraph of the editorial concedes the strong evidence that the most effective treatment for CRF is exercise, although the citations omitted the Cochrane collaboration review that yields even larger effect sizes for longer follow up. Instead, tertiary sources are cited for lower estimates of the efficacy of exercise. The implication of exercising being the most effective treatment is blunted by following up with citations of meta-analyses for psychological interventions that find small effects, but at least the largest effect for psychological interventions reported in a meta-analysis matches the smallest effect found for exercise. I have reviewed in detail one of these meta-analysis for psychological interventions and found it horribly deficient as a systematic review and integration of data. See for yourself here.

Having collapsed differences in effectiveness of interventions for fatigue, the next paragraph declares

it would be reasonable to recommend physical activity to patients during and after cancer treatment (preferably under supervision of a rehabilitation professional) and provide them with tired education about CRF. However, we do not know whether these strategies will be helpful for patients with more severe or persistent fatigue, given that very few intervention studies have specifically targeted these patients.

Why the parenthetical “under supervision of a rehabilitation professional”? Exercise is a lifestyle activity that does not necessarily require a professional, an aerobics class will do. However, free or low-cost lifestyle activities threaten legitimizing third-party payments for other activities that are unlikely to be as effective. What is going on here is the reframing of exercise as not just an activity, but an evidence-based treatment requiring a professional. This is a move in the game of establishing yoga and acupuncture as evidence-based i.e., reimbursable treatments when provided by a professional.

There are lots of reasons for cancer patients to do yoga or to exercise, other than to reduce cancer related fatigue. The idea of making these activities into treatments reimbursable by third-party payers might at first seem attractive to yoga teachers and aerobics instructors and consumers alike. However, the medicalization of such activities inevitably brings the bureaucracy of credentialing, and then licensing, required workshops and continuing education, etc. These costs are passed onto consumers, not all who have suitable insurance. The net result is that formally free or low-cost activities become more expensive and less accessible.

The editorial recommends extending evaluation of exercise with patients having  moderate to  severe fatigue. There may be practical problems in doing so, such as more severe fatigue being associated with more severe pain that would inhibit patients from adhering to regular exercise, as well as the problem of other cancer and non-cancer related morbidities, but nonetheless worth a try. But this is not where this editorial is going….

The next paragraph flies up to the thin air of the woo-osphere. Stating that there are only a handful of RCTs targeting patients with moderate or severe fatigue, it cites some cognitive behavioral therapy studies that get modest effects, but also–here it comes–integrative medicine approaches (yoga, biofield therapy, mindfulness-based therapy) that may have beneficial effects. More foundation is being laid for an acupuncture study. But let’s look at the citations for integrative medicine approaches.

The first citation is to a study of yoga conducted by the author of the editorial. Missing is any citation of a meta-analysis that concludes that a flawed literature reveals only small effects for yoga for fatigue associated with chronic illness and that a considerable proportion of studies have significant differences between patients assigned to the intervention versus control conditions. The editorial author’s own yoga study is another small study (31 patients) of Iyengar yoga techniques emphasizing

postures and breathing technique, believed to be effective for reducing fatigue among women with a history of breast cancer, with a focus on passive inversions (i.e., supported upside-down postures in which the head is lower than the heart) and passive backbends (i.e., supported spinal extensions). In supportive postures, the shape of the pose is supported by props. (i.e., blocks, bolsters, blankets, wall ropes, belts) rather than being held by the strength of the body, so that participants can perform, and maintain the postures without stress and tension).

Participants were self-selected for interest in yoga, based on responses to mailings, advertisements, and flyers. The control group received didactic health education classes that were not matched in frequency or duration to the yoga being provided to the women assigned to that condition. Maybe upside down-postures and backbends reduce fatigue by some mysterious, unarticulated mechanisms, but maybe, consistent with studies of exercise, yoga is a structured way of getting activated and stronger with the necessary support and attention to keep participants on track. Unlike the appeal to the wisdom of the ages concerning yoga, this possibility is testable and potentially disconfirmable with a RCT with a suitable control condition.

The second citation is to an unbelievable bit of woo science, a RCT of therapeutic touch (TT) for CRF that actually yielded null findings for fatigue. The article describes TT as targeting “energy fields that purportedly surround and penetrate the human body for the purposes of healing,” and assumes that it reduces fatigue by improving the immune system. The intervention was chosen by the one authors Reverend Rosalyn L. Bruyere of the  Healing Light Center Church who is described elsewhere as having extensively studied Egyptian temple symbology, sacred geometry, shamanic practices, pre-Buddhist Tibetan Bon-Po Ways, and various Native American Medicine traditions. The control condition consisted of practitioners of TT administering it without the (mental) intention of affecting energy fields. Christoffer Johanssen, David Gorski and myself published a scathing critique in Cancer of the study and David also covered it in a Science Based Medicine blog post.

The third citation is to a modest study of mindfulness-based therapy that found differences between a mindfulness therapy that aimed to help patients become more aware of and inhibit potentially maladaptive responses and a waitlist control in analyses that had differential retention of intervention and control patients.

In the next paragraph, the editorial gets to its raison d’etre, a commentary on the RCT of acupuncture it is intended to introduce. The segue is that this RCT addresses this gap in the literature, i.e. the lack of studies with patients with at least moderate fatigue. Some basic details of the RCT are presented, but then editorial flies back up to the woo-osphere:

findings from a study by Molassiotis et al, together with earlier trials, provide compelling evidence that acupuncture may be effective for reducing CRF, at least in the short term, it will be important to determine how enduring the effects of this treatment are, given that only the immediate post-treatment effects were described this report and to identify the frequency and duration of acupuncture that are necessary for improvement.

Note the incoherent hedging that I highlighted with italicizing… If these three studies are so compelling, why the hedge may be effective? Anyone who has ever criticized premature and exaggerated claims of PNI and CAM will recognize this clever defensive strategy. If critics take aim at the claim of compelling evidence, they will be neutralized by being reminded of the may be.

So now the editorial has arrived at a declaration in JCO, even if incoherently hedged, that the evidence for acupuncture is compelling, advancing requests for reimbursement and a call for the urgency to further research of acupuncture for fatigue that can be cited in a NCAM proposal.

The Molassiotis et al study compared self-referred patients answering ads for an acupuncture study who actually got acupuncture versus those who got a booklet. This was no control for the positive expectations, ritual, attention, support, and feedback that might account for any differences, which could have been achieved with a sham acupuncture condition administered by interventionists blinded as to whether they were providing a sham condition.

The JCO article reporting the Molassiotis et al study conceded that it was unknown why acupuncture might work for fatigue, but strongly advised against any study comparing acupuncture and sham acupuncture:

a sham acupuncture needling method was not included because of debate surrounding sham methods. It is increasingly believed a sham controlled trial is only appropriate when two acupuncture interventions are compared. In addition, sham acupuncture designs cannot detect the whole placebo effect, may generate false-negative results,21-24 and may introduce ethical and practical dilemmas.25 Experimental and clinical studies have also shown that minimal or sham acupuncture used as placebo control is not necessarily inert from a physiologic perspective, and its relevance as placebo acupuncture must be questioned,26,27 even when it is not used as per acupuncture principles.22,28 Instead of reducing bias, sham designs may introduce bias against the treatment being tested.29 To regard placebo acupuncture as a universally effective super placebo would be inappropriate, and results should be interpreted with care.30

Me thinks Molassiotis and colleagues doth protest too much. What about bias in favor of acupuncture, and risk of false positive results when a sham condition is not provided? What about the ethical and practical dilemmas of offering acupuncture if it is no better than a sham treatment? But before you get worked up and write a critical letter to JCO, remember that Molassiotis or colleagues can simply block it getting published by refusing to respond.

Characteristically for such editorials in JCO, this one does not really offer any serious criticisms of the RCT it accompanied. The editorial concludes

what advice can we offer patients with persistent fatigue? Acupuncture may be helpful, particularly for women with nonmetastatic breast cancer, though patient should be urged to follow the specific protocol that was found to be safe and effective in the study by Molassiotis et al.

Ah, the hedge again that I italicized, but why the urging that the specific protocol of Molassiotis et al. be followed? It comes down to the silly ritualism of promoting CAM with calls for rigid adherence to specific procedures, whether they be variants of yoga, biofield touch therapy, or acupuncture. Accept no substitutes. Such rigid adherence allows distinguishing between what is proposed for reimbursement and what cannot because it is untested.  No matter that such specificity in procedures or even a credible putative mechanism for this versus that procedure has been established.

Posted in: Acupuncture, Cancer, Clinical Trials, Energy Medicine, Neuroscience/Mental Health, Traditional Chinese Medicine

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